Effects of a combined oral contraceptive containing oestradiol valerate/dienogest on hormone withdrawal-associated symptoms: Results from the multicentre, randomised, double-blind, active-controlled HARMONY II study

Abstract

The objective of this multicentre, randomised, double-blind study was to compare a combined oral contraceptive (COC) containing oestradiol valerate/dienogest (E₂V/DNG) administered in a dynamic dosing regimen with a monophasic COC containing ethinyloestradiol/levonorgestrel (EE/LNG), with regard to their ability to reduce the frequency and intensity of headache and pelvic pain in women with hormone withdrawal-associated symptoms (HWAS). Women aged 18–50 years received E₂V/DNG in an oestrogen step-down and progestin step-up regimen (26/2 regimen; n = 223) or EE 20 μg/LNG 100 μg (21/7 regimen; n = 218) over six cycles. Headache and pelvic pain were assessed using a visual analogue scale (VAS) during cycle days 22–28. Rescue medication use was also assessed. E₂V/DNG was superior to EE/LNG with regard to reducing the frequency and intensity of headache and pelvic pain from baseline to cycle 6 (change from baseline in the average of the three highest VAS values [mean ± standard deviation]: 47.7 ± 29.4 vs 34.5 ± 25.7 mm, respectively; p < 0.0001). The use of rescue medication was also significantly reduced with E₂V/DNG compared with EE/LNG (p < 0.05). E₂V/DNG may be a good option for women who experience HWAS with traditional 21/7-day regimen COCs.

Keywords::

• Dienogest
• HARMONY II
• headache
• hormone withdrawal- associated symptoms
• oestradiol valerate
• oral contraception

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Erratum

Declaration of interest: Funding for this study was provided by Bayer HealthCare. Medical writing assistance was provided by Clare Wheatcroft and Richard Glover of inScience Communications, Springer Healthcare. The funding for this assistance was provided by Bayer HealthCare.

Gerardo Macìas is a principal investigator (external) at the Mexican Institute of Clinical Research, México City, México, which received financial support for conducting clinical trials from Bayer HealthCare.

Gabriele Susanne Merki-Feld has financial relationships (paid lecturer and advisory board member, research support) with Bayer Healthcare and Merck, Sharp & Dohme Corp.

Susanne Parke, Uwe Mellinger and Marco Serrani are all employees of Bayer HealthCare, Berlin, Germany.

ClinicalTrials.gov identifier: NCT00778609